Values of restricted normalized isotropic (RNI) scaling factor, a brain microstructural marker that may suggest neuroinflammation, were associated with age and BMI among youths with varying weight gain, with a robust association with greater increases in BMI in young girls, according to research published July 23 in JAMA Network Open.

Using data from the Adolescent Brain Cognitive Development Study, Shana Adise, PhD, et al., analyzed brain scans from 1,855 youths aged nine to 20 years (mean baseline age, 119 months) with a healthy weight at baseline (BMI percentile <85th).

Investigators focused on the subcortical regions of the brain due to their involvement in food intake regulation and used restriction spectrum imaging fitted to diffusion-weighted imaging data to extract RNI scaling factor estimates. RNI measures spherical water diffusion within neuronal and glial cell bodies, serving as a potential marker of neuroinflammation.

At the two-year follow-up, 1,072 participants were classified as healthy-weight, weight-stable (HW-WS) and 775 as healthy-weight, non-weight-stable (HW-NS) defined as weight change of one standard deviation or more. In the groups, about half were female and the mean age at baseline vs. year two was about 119 vs. 143 months.

Results showed that, among HW-WS youths, greater RNI values were associated with older age but not BMI, which investigators state could be related to the synaptic pruning that comes with adolescent neurodevelopment.

However, among HS-NS youths, RNI values and BMI had bidirectional associations across many subcortical regions independent of age. Greater RNI values also corresponded with greater increases in BMI among girls and young women.

"This study provides additional support for the idea that neurobiological factors, such as potential neuroinflammation, may underlay and/or promote weight gain due to potential dysregulated appetitive control and its associated cognitive and metabolic consequences," write the authors.

In an accompanying editorial comment, Peter A. Hall, PhD, marks a "missed opportunity" for the study to have included weight circumference as an additional obesity metric, and suggests that the relationship between adiposity and neuroinflammation could be further studied in clinical trials, especially with drugs like GLP1-RA medications that impact neuroinflammation.